Sulphonium compounds



United States Patent" SULPHONIUM COMPOUNDS Frank Peter Doyle and Edward Raymond Stove, Brockham Park, Betchworth, England, assignors to Beecham Research Laboratories Limited, Betchworth, England, a British company No Drawing. Application November 19, 1956 Serial No. 622,827

Claims priority, application Great Britain November 28, 1955 9 Claims. (Cl. 260-501) R R a have marked hypotensive activity (as measured in laboratory animals). It has been found that such marked bypotensive activity is present in the series in those cases in which 12:4, or 6, especially 4 or 5.

In the general Formula I, R, R R R and R are the same or different, and each of which is an alkyl group, and X is an anion.

The novel compounds of the present invention are those in which n=4, 5 or 6, preferably 4 or 5, and the total number of carbon atoms in the cation is from 11 to 16 inclusive, and preferably from 13 to 15 inclusive.

Accordingly, the present invention provides novel compounds of the general Formula I in which 1124, S or 6, preferably 4 or 5, R, R R R and R are the same or difierent and each of which is an alkyl group, and X is an anion, the total number of carbon atoms in the cation being from 11 to 16 inclusive and preferably from 13 to 15 inclusive.

The compound of the general Formula I in which n=4, R=R =R =R =R=Me prepared by Schneider and Kaufmann (Annalen, 1912, 392, 10) by fully methylating the amine CH .S. (CH .NH (II) with methyl iodide in the presence of sodium methoxide has only very slight activity whereas the compound of ice 2 the general Formula'l in which n=4, R=R =R==R R ==Et, whose preparation is described in Example 1 below, is very active-as a hypotensive agent.

The nature of the anion X- is not of primary importance .and may be chosen from any of the usual accepted groupings such as halide, sulphate or tartrate, the choice depending upon pharmaceutical convenience and the physical properties (stability, solubility, etc.) desired, although of course toxic anions such as the oxalate ion should be avoided. The preparation of organic acid salts from the halide salt may be carried out by reaction with the silver saltof the appropriate acid or by reaction with the appropriate acid in presence of ethylene oxide (cf. Sackur, Bull. Soc.'chim., 1952, 796).

The preferred compounds of Formula I are the salts of 1 diethylsulphonium 4 triethylammoniumbutane, 1 ethylmethylsulphonium 4 triethylammoniumbutane, 1 ethylmethylsulphonium 4 ethyldi n propylammoniumbutane, l dimethylsulphonium 4 methyldiisopropylammoniumbutane, l ethylmethylsulphonium- 4 methyldi-isopropylammoniumbutane, 1 methylisopropylsulphonium 4 methyldiisopropylammoniumbutane, 1 dimethylsulphonium 4 methyldi n propylammoniumbutane, 1 diethylsulphonium 5 triethylammoniumpentane, and 1 ethylmethylsulphonium-S- ethyldi-n-propylammoniumpentane.

The novel compounds of the present invention may be prepared by treating an appropriate di-N-substituted alkylthioalkylamine or a mono-quaternary salt thereof with an excess of a quaternising agent such as methyl iodide, with or without a diluent such as acetone or alcohol.

The term quaternising agent as used herein refers to an agent which renders the nitrogen atom quaternary and/ or the sulphur atom ternary.

The di-N-substituted alkylthioalkylamines (cf. general Formula III below), in which the total number of carbon atoms is from 9 to 14 inclusive, preferably from 11 to 13 inclusive, are new compounds and may be prepared by the reaction of the appropriate haloalkylamine as its hydrohalide salt (usually the chloroalkylamine as its hydrochloride) with a metal salt of an alkanethiol (usually in excess) in a solvent (usually ethanol). (Cf. Brighton and Reid, J. Amer. Chem. Soc., 1943, 65, 458; Andrews, Bergel and Morrison, J. C. S., 1953, 2998, and Kirchner, Soria and Cavallito, J. Amer. Chem. Soc., 1955, 77, 4599.)

An alternative route for the preparation of di-N-substituted alkylthioalkylamines is the conversion of the appropriate di-N-substituted hydroxyalkylamine" to the thioalkylamine by the action of hydrobromic acid and thiourea (cf. Frank and Smith, J. Amer. Chem. Soc., 1946, 68, 2103; Plant, Tarbell and Whiteman, ibid, 1955, 77, 1572) followed by basification and alkylation of the thiol group thus formed by the usual methods.

aswaaea The following reaction scheme illustrates how the compounds may be prepared:

lR X MOEt Ra R B(CH:)nN MK EtOH (III) lax Rt R2 I t S. ((3111),..171-12. 2X R R The following examples illustrate how the process of the invention may be carried into effect.

Compounds where n=4:

EXAMPLE 1.--1DIETHYLSULPHONIUM 4 TRI- ETHYLAMMONIUMBUTANE DI-IODIDE Method 1.Ethyliodide (4.9 ml.) was added to solution of 4-ethylthiobutyldiethylamine (1.9 g.) in dry acetone ml.) and the resulting solution stirred under reflux on a water bath for 8 hours. After removal of the first crop of crystalline material (2.2 g.) M. P. 143 C. (decomp.) the mother-liquor was refluxed for a further 14 hours to give a second crop (1.1 g.) M. P. 139-140" C. (decomp.). The combined yield (3.3 g.) was recrystallised from ethanol (10 ml.) to give colourless prisms (2.9 g., 59%) M. P. 142 C. (decomp.). (Found: C, 33.4; H, 6.5; I, 50.3. C H NSI requires: C, 33.5; H, 6.6; I, 50.6%.)

The dihydro'gentartrate salt was prepared by shaking an aqueous solution of the di-iodide (1 mole) with a slurry of neutral silver tartrate (1 mole) in aqueous tartaric acid (1 mole). The precipitated silver iodide was removed by filtration, the filtrate concentrated in vacuo (water pump) and the semi-solid white crystalline mass dried in vacuo (no desiccant) to give white crystalline powder (97%) M. P. 103-104 C. Recrystallisation from 95% v./v. ethanol gave clusters of colourless needles of the dihydrate M. P. 103-105" C. (Found: C, H, S, 5.9. C23H43012NS. requires: C, 45.45; H, 8.1; S, 5.5%.)

An alternative method for the conversion of the di- 4= iodide to the, di-hydrogentartrate follows. that described by Sackur (loc. cit.) in which the di-iodide (1 mole) and tartaric acid (3 moles) in warm concentrated alcoholic solution were treated with ethylene oxide (4 moles). The di-hydrogentartrate precipitated and was purified as described above.

Method 2.Ethyl iodide (0.81 ml.) was mixed with 4-ethylthiobutyldiethylamine (1.9 g.) and the mixture allowed to react for 7 days at room temperature without solvent. The resulting solid was digested with dry ether, collected by filtration and purified by dissolving in acetone (5 ml.) and precipitating with dry ether (10 ml.) to give 4-ethylthiobutyltriethylammonium iodide as colourless needles (2.0 g., 58%), M. P. 97 C. (Found: C, 42.1; H, 8.0; I, 36.8. C H NSI requires: C, 41.7; H, 8.1; I, 36.8%.)

Ethyliodide (2.0 ml.) was added to a solution of 4- ethylthiobutyltriethylammonium iodide (1.8 g.) in warm dry acetone (10 ml.) and the resulting solution stirred under reflux on a water bath for 24 hours. The solution was cooled, the product collected by filtration (2.0 g., 76%) and crystallised from ethanol to give colourless prisms, M. P. 138140 C. (decomp.). (Found: I, 50.6%.)

' 4-ethylthz'obutyldiethylamine Method A.-4-chlorobutyldiethylamine hydrochloride.-A solution-of thionyl chloride (97 ml.) in dry chloroform (200 ml.) was added to a stirred solution of 4-hydroxybutyldiethylamine (156 g.) (Avison, J. Appl. Chem. 1951, 1, 469) in dry chloroform 160ml.) with external cooling (solid carbon dioxide bath). The mixture was allowed to warm to room temperature, refluxed for 0.5 hour, and then concentrated initially at normal pressure, and finally in vacuo, to remove traces of chloroform. The residual oil was azeotroped twice with dry benzene and then cooled when it crystallised. The pro duct was used in the next stage of the synthesis without further purification.

4-ethylthiobutyldiethylamine Ethyl mercaptan (290 ml.) was added to a cooled solution of sodium (89 g.) in ethanol (2 1.). The solution was brought just to reflux temperature and 4- chlorobutyldiethylamine hydrochloride (the total crude yield from above) in ethanol (550 ml.) added over about 1 hour. The mixture was refluxed for 2 hours and the alcohol was then distilled as completely as possible from a boiling water bath (normal pressure). The residue was cooled, diluted with water (1.5 l.) and extracted with ether (3 x 1 1.). The combined extracts were washed with water (3 x 250 ml.), dried (MgSO concentrated and distilled in vacuo to give the product as a colourless oil (172.8 g., 87%) B. P. -113 C./10 mm., 1 1.4705. (Found: C, 63.6; H, 12.3; S, 16.9. C H NS requires: C, 63.5; N, 12.2; S, 16.9%.)

Method B.--4-mercapt0butyldiethylamine.-4-hydroxybutyldiethylamine g.) was added with stirring to 48% hydrobromic acid (350 ml.). Thiourea (91 g.) was then added, and the mixture refluxed for 8 hours. The solution was cooled and, in an atmosphere of nitrogen, caustic soda solution (160 g. NaOH, in 640 ml. water) was added, and the mixture refluxed for 2 hours under nitrogen. The oily layer was separated, combined with 7 x ml. ether extracts of the aqueous layer which were then dried, concentrated, and distilled in vacuo to, give the product as a colourless oil (113 g., 70%) B. P. 95-96 C./15 mm. 1, 1.4678.

4-ethylthi0butyldiethylamine 4-mercaptobutyldiethylamine (161 g.) was added to a cooled solution of sodium (23 g.) in ethanol (460 ml.),

refluxed-for 3- hours. The reaction mixture was filtered to remove the precipitated sodium bromide, the filtrate concentrated, filtered, and distilled in vacuo to give the product (152 g., 80%) as a colourless oil.

EXAMPLE 2.-1-ETHYLMETHYLSULPHONIUM-4- 'TRIETHYLAMMONIUMBUTANE DI-IODIDE Ethyl iodide (8.4 ml.) and 4-methylthiobutyldiethylamine (3.0 g.) were allowed to react together in nitromethane (8.4 ml.) for 1 week at room temperature. Dry ether (25 ml.) was added, the oily product was allowed to settle, and supernatant nitromethane/ether layer was removed and replaced by. acetone. The product was induced to crystallise and was then recrystallised twice from n-butanol (40 ml.) at 75 C. to give a pale yellow deliquescent crystalline solid (3.3 g., 40%) M. P. 114-116 C..(decomp.). (Found: C, 31.8; H, 6.9; S, 6.6; I, 52.0. C H NSI requires: C, 32.1; H, 6.4; S, 6.6; I, 52.1%.)

' .4-methylthi0butyldiethy'lamine 4 chlorobutyldiethylamine hydrochloride prepared from 4-hydroxybutyldiethylamine (11.9 g.) and thionyl chloride (7.4 ml.) as in Example 1, Method A, was dissolved in ethanol (40-ml.) and added over a period of:

about minutes to ethanolic sodium methane thiol (147 ml. of the solution prepared as described in Organic Syntheses, Coll. Vol. II, p. 345, and containing 1' mole in 460 ml.) which had been brought just to reflux temperature. hours and then the alcohol was distilled as completely as possible from a boiling water bath (normal pressure).'

The residue was cooled, diluted with water (200 ml.) and extracted with ether (3 x 100 ml.). The combined extracts were washed with water (3 x 40 ml.), dried (MgSO concentrated, and distilled in vacuo to give the product as a colourless oil (12.1 g., 86%) B. P. 108112 C./19 mm. 1 1.4718. Styphnate M. P. 71-73 C. from ethanol. (Found: C, 42.9; H, 5.9; N, 13.2. C H N 0 S requires: C, 42.8; H, 5.7; N, 13.3%.)

EXAMPLE 3. l-ETHYLMETHYLSULPHONIUM-4- ETHYLDI n PROPYL AMMONIUMBUTANE DI-IODIDE Ethyl iodide (4.9 ml.) was added to a solution of 4- methyl-thiobutyldi-n-propylamine (2.0 g.) in dry acetone ml.) and the resulting solution allowed to stand at room temperature for 2 months. The supernatant acetone layer was decanted, the oily product washed with dry acetone (20 ml.), and the product allowed to stand cov' ered with further dry acetone (20 ml.) for several hours when it crystallised (2.3 g., 45%), M. P. 10l-104 C. (decomp.). Recrystallisation from n-propanol, gave colourless crystals, M. P. 9.8101, C. (decomp. 112 C.).

(Found: C, 35.3; H, 7.1; I, 49.1. C H NSI requires:

C, 35.0; H, 6.8; I, 49.3%.)

4-methylthiobutyldi-n-propylamine Reaction of B-carbomethoxypropionyl chloride (1i mole) with di-n-propylamine (2moles) in dry ether gave methyl N:N-di-n-propylsuccinamate as an almost colour-- The mixture was refluxed for 2 6 EXAMPLE 4. l DIMETHYLSULPHONIUM 4- METHYLDI ISOPROPYL AMMONIUMBUTANE- DI-IODIDE requires: C, 32.0; H, 6.4; I, 52.5%.)

4-methylthiobutyldi-isopropylamine Reaction of B-carbomethoxypropionyl chloride (1 mole) with di-isopropylamine (2 moles) in dry ether gave methyl-N:N-di-isopropylsuccinamate as an almost colour- EXAMPLE 5.-1-ETHYLME'IHYLSULPHONIUM-4- METHYLDI ISOPROPYL AMMONIUMBUTANE DI-IODIDE Methyl iodide (2.5 ml.) was added to a solution of 4- ethylthiobutyldi-isopropylamine (2.2 g.) in dry acetone (20 ml.) and the resulting solution allowed to stand at room temperature for 24 hours. The product was collected by filtration (4.5 g.), recrystallised twice from isopropanol (10 ml.), and further purified by dissolving in nitromethane (3 ml.) and precipitating with dry acetone (10 ml.) This latter procedure was carried out three times to give deliquescent colourless microprisms (1.0 g., 20% M. P. 141 C. (decomp.). (Found: C, 33.8; H, 6.8; S, 6.1; I, 50.5. C H NSI requires: C, 33.5; H, 6.6; S, 6.4; I, 50.6%.)

4-'ethylthiobutyldi-isopropylamine 4-chlorobutyldi-isopropylamine hydrochloride (see Example 4) was reacted with sodium ethane thiol as in Example 1, Method A, to give 4-ethylthiobutyldi-isopropylamine as a colourless oil, B. P. 136-137 C./16 mm. 1 1.4657. (Found: C, 65.9; H, 12.4; N, 6.8. C H NS requires: C, 66.4; H, 12.5; N, 6.5%.)

EXAMPLE 6. 1 METHYLISOPROPYLSULPHO- NIUM-4-METHYLDI-ISOPROPYLAMMONIUMBU- TANE DI-IODIDE Methyl iodide (2.5 ml.) and 4-isopropylthiobutyldi-isopropylamine (2.3 g.) wereallowed to react together in nitro'methane (10 ml.) for 4 days. The product was collected by filtration (3.0 g.) and recrystallised, first from nitro-methane (4.5 ml.) on a boiling water bath and then from 96% v./v. aqueous isopropanol (16.5 ml.) to give colourless rods (0.9 g., 17%), M. P. 163164 C. (decomp.). (Found: C, 34.6; H, 7.1; S, 6.1; I, 49.7.

C H NSI requires: C, 34.9; H, 6.8; S, 6.2; I, 49.3%.)

4-isopr0pylthiobutyldi-isopropylamine 4-chlorobutyldi-isopropylamine hydrochloride (see Example 4) was reacted with sodium isopropane thiol to give 4-isopropylthiobutyldi-isopropylamine as a colourless oil B. P. 133-136 C./10 mm. 1.4662. (Found: C,

67.3; H, 12.4; N, 6.2. C H NS requires: C, 67.5;

Similar methods were employed for the preparationof the compounds shown in the following examples:

aeaaaee Example Formula Reaction Conditions for Recrystallisation Solvent and Analysis N o. Quaternisation M.P.

"Me Me 7 F S (CHflgN-MB F In acetone at room temp. n-Butanol at 90-100" 0., M.P. 130- {Found: C, 29.1; H, 6.4; I, 55.3%.

' for 1 week. 131 C. (decomp.). Deliqnes- Requires: .0, 28.8; 5.9; I, 55.4%. .Et Et cent.

8 1" MenS (CHn)4N-Et I In acetone at room temp. Ethanol, M.P. 111l15 C. (de- {Found: 0, 29.0; H, 6.1; I, 55.1%.

' \Et for 1 day. comp). Deliquescent. Requires: 0, 28.8; H, .9; I, 55.4%.

9 1 EMS (CH:)4NMe 1" In acetone at room temp. n-Butanol at 120-100 0., M.P. 107- {Found: 1, 53.5%.

. \Et for 18 days. 111 C. (decomp.). Requires: I, 53.6%.

'Me\ /Me I 'I- V 10 I' S (CH:)4N-Et I" In acetone at room temp. n-Butanol at 7080 0., M.P. 110- {Found: C, 30.6; H, 6.1; I, 53.5%.

for 1 day. 114 0. (decomp.). Deliques- Requires: 0, 30.4; H, 6.1;1, 53.6%. Et Et cent.

4 11.; I M6aS(CH2)(NP1 1' In acetone at room temp. Ethanol, M.P. 129-130' C. (de- {Found: 0, 31.9; H, 6.6; I, 52.0%.

' for 5 days. comp.), M.P. Ill-113 C. (de- Requires: 0, 3 .0; H, 6.4; I, 52.2% Pr'= comp.) (dimorphic).

F'Me /Me 12 I S ((3H;).;NPr I do n-Butanol at approx. 90 0., M.P. Found: C, 34.7; H, 6.9; I, 49.3%.

9193 C. Deliquescent. Requires: 0, 34.9; H, 6.8; I, 49.3%. Pr Pr"- 13 Br M8aS(CHz)4N-Bl1 Br In acetone at room temp. Dissolved in n-butanol at approx. I Found: C, 42.5; H, 8.6; Er, 38.1%

for 1 day. 70 C. and pptd. with acetone, (Requires: 0, 4 .7; H, 8.3; Er, 38.0% Bu M.P. 111-114 0. (decomp.).

Deliquescent. "E1: Et

v 14 I S (CHg)4NEt I In acetone at room temp. Dissolved in n-butanol at approx. {Found: C, 36.0;H, 7.4; I, 47.4%.

for 50 days. 70 C. and ptd. with ether, Requires: 0, 36.3; H, 7.0; I, 48.0%. Pr Pr M.P. 100-102 C. (decomp.).

ACTIVITY (EFFECT ON THE BLOOD PRESSURE OF NORMOTENSIVE RATS) OF THE EXAMPLES WHERE n=4 Compounds where n=5:

EXAMPLE l5.--l-DIETHYLSULPHONIUM-S-TRL ETHYLAMMONIUMPENTANE DI-IODIDE Ethyl iodide (24.3 ml.) was added to a solution of 5- ethylthioamyldiethylamine (10.0 g.) in dry acetone (100 ml.) and the resulting solution, after being stirred under reflux on a water bath for 8 hours was allowed to cool. The product was collected by filtration and recrystallised vfrom ethanol (168 ml.) to give colourless plates (17.5 g.,

68%), M. P. 160-161 C. (decomp.). (Found: C, 35.0; H, 6.8; I, 49.6. C I-I NSI requires: C, 35.0; H, 6.8; I, 49.3%.)

5-ethyllhioamyldiethylamine S-chloroamyldiethylamine hydrochloride (Chem. Abs, 1934, 28, 1770) was prepared from 5-hydroxyamyldiethylamine (Avison, loc. cit.) and reacted with sodium ethane thiol as in Example 1, Method A, to give S-ethylthioamyldiethylamine as afaintly straw-coloured oil, B. P. 113 C./5 mm. 1 1.4702. (Found: C, 65.0; H, 12.5; N, 7.2. C H NS requires: C, 65.0; N, 12.3; N, 6.9%.) EXAMPLE v16. l-ETHYLMETHYLSULPHONIUM- S-ETHYL-Dl n PROPYLAMMONIUMPENTANE DI-IODIDE Ethylipdide (4.9 -rnl.) was added to a solution of 5-methylthioamyldi-n-propylamine (2.2 g.) in dry acetone (20 ml.) and the resulting solution allowed to stand at room temperature for 1 month. The product was collected by filtration (4.8 g.) and recrystallised from n-propanol (9 ml.) at -95 C. to give small colourless rods (3.6 g., 68%), M. P. 126-127 C. (decomp.). (Found: C, 36.2; H, 7.4; I, 48.3. c,,H,.,NsI, requires: C, 36.2; H, 7.0; I, 48.0%.)

S-methylthioamyldi-n-propylamine Reaction of -y-carbomethoxybntyryl chloride (1 mole) with di-n-propylamine (1 mole) in the presence of triethylamine (1 mole) in dry ether gave methyl-NzN-di-n-propylglutaramate as a colourless oil, B. P. C./0.7 mm., 1 1.4580. Reduction of the latter with lithium aluminium hydride (1.5 moles) gave S-hydroxyamyldi-npropylamine as a colourless oil, B. P. 122-126 C./7 mm. 1 1.4545. This was converted via S-chloroamylcli-npropylarnine hydrochloride as in Example 2, to S-uiethylthioamyldi-n-propylamine, a colourless oil, B. P. 141 C./13 mm. 1 1.4654. (Found: C, 66.0; H, 12.2; S, 14.8. C H NS requires: C, 66.4; H, 12.4; S, 14.7%.)

Similar methods were employed for the preparation of the compounds shown inthe following examples:

Example Formula Reaction Conditions for Recry stallisation solveut and Analysis No. Quaternisation M.P.

"Me Me a 1 F S(CH)| Me 1' In acetone at room temp. "Ethanol, M.P. 155-157 0. (de- Found: 0, 30.4; H, 6.1; I 53.4%. m:/ \EIt ior2weeks.. I vcomp.). Requires: 0, 30.4; E, 6.1; 53.6%.v

Me 18 I M0|S(CH1)sNEt I In acetone at room temp. Ethanol M. P. 144-148 0. (de- Found: 0, 30.3; H 6.3; I, .5%. iorlday. comp-5. RequireszO, 30.4; h, 6.1; I, 53.6%

';'Me Me H 19 v I S(CH|)uN-Et I" Ethanol M. I. 136--138 0. (de- {Found: C, 32.3; H, 6.6; I,-'62. 2%.

. compj. Requires: 0, 32.0; H, 6.4; I, 52.2%. Et Et Me I 20 I M9zS(CHa)|N-Pr I Inacetone at room temp. n-Proganol at 2a ppi'ox. 70'O., Found: 0,315.9;11, 6.9;I, 50.4%.

. forlmonth. M. 11011 0. (decomp.). Requires: 0,113.5; H, 6.6; I, 50.6%. 131:" Deliquescent.

ACTIVITY (EFFECT ON THE BLOOD PRESSURE 0F NORMOTENSIVE v EATSiOF THE EXAMPLES WHERE n= Example Total Example Total No. Carbon Activity N 0. Carbon 7 Activity Atoms v Atoms Hexamethonium. "12 Hexamethonium. 1 16 o. I 13; Hexamethonium. 12 Hexameth'onium. 14 Hexamethonium.

Compounds Where 3 6: The following examplesfiere'" prepared by methods similar to those already described 1' for the compounds where n=4 and n=5. 1

Example Formula Reaction Conditions" for Recrystellisation Soluentand I Analysis N Quatemisation M.P.

21 I Me;S(CHz)uNMe; 1" Room temp. for 1 day Ethanol, M.P. 158-160 0. (de- {Found: 0, 290,H, .2; N, 2.7, S, 7.1%. M without other solvent. comp.) Requires 0, 28 8; H, 5.9; N, 3.1, S, 7.0%.

Q 22 I (CHz)eNM8: I In acetone at room temp. Ethanol, M.P. 117-120" C. (de- {Found C, 30.3, H, 6 3; I, 53.4%.

Et for2days. comp.). Requires: 0, 30.4; H, 6.1; I, 53.6%

"Me Me 23 I S(CH|)uNMe I In acetone at room temp. Ethanol, M.P. 89-91 C. (de- {Found: C, 31.9; H, 6.3; N, 2.8%. Et/ \Et for 8 days. comp.). Requires: 0, 32.0; H, 6. N, 2.9%. "Me\ /Me 4- 24 I (CHz)|NEt I In acetone at room temp. Ethanol, M.P. 110-114 C. (de- {Foumh C, 33.6; H, 7.0; I, 50.9%.

Et/ \Et for 1 day. comp.). Requires: 0, 33.5; H, 6.6; I, 50.6%.

Me 25 1 En (CH|)| Me I" In acetone at room temp. Ethanol, M.P. 118-121 C. (de- {Found: C, 33.7; N, 6.9; I, 50.4%.

\Et for 15 days. comp.). Requires: 0, 33.5; H, 6.6; I, 50.6%. "Me\ /Me 26 1- wmnfi-m r In nitromethane at room iso-Propanol, M.P. 110-114" 0. {Found: 0, 35.2; H, 7.1; I, 49.0%.

I \:P i temp. for 6 weeks. (decomp.). Requires: 0, 34.9; H, 6.8, I, 49.3% r 1' Me Me 27 I S(CH2)eN-Me F In acetone at room tem n-Propenol at 90 0., MP. 103- Found: 8, 6.7; I, 49.1%.

i'or 2rnonths or at 104 0. Requires: 5, 6.2; I. 49.3%. Pr Pr" for 10 days.

'Me\ /Me 7 28 I (CHa)uN-Me 1 Room temp. for 4 days n-Butanol at -100 0., MP. Found: C, 37.3; E, 7.4; I, 46.7%.

without other solvent. 153155 O. (decomp.). Requires: 0, 37.6; H, 7.2; I, 46.8%. Bu Bu 29 I[Eta (CHmNEtJI' In acetone at room temp. Ethanol, lVLP. 141 C. (de- {FOilIidI C, 36.6; H, 7. I, 47.8%

ior2months. comp.). Requires: 0, 36.3; H, 7 0; I, 48 0% ACTIVITY (EFFECT ON THE BLOOD PRESSURE OF NORMOTENSIVE BATS) on THE EXAMPLES WHERE n= 6 We claim: v 1. Compounds of thegeneral formula:

in which n is aninteger of from 4 to 6 inclusive, R, R R R and R are each an alkyl group, and X is a nontoxic anion, the total number of carbon atoms in the cation being from 11 to 16 inclusive.

2. Compounds of the general formula:

in which n is an integer of from 4 to 6 inclusive, R, R

R R and R are each an alkyl group, and X is va nontoxic anion, the total number of carbon atoms in the cation being from 13 to 15 inclusive.

3. Compounds of the general formula:

in which R, R R R and R are each an alkyl group and X is a non-toxic anion, the total number of carbon atoms in the cation being from 11 to 16 inclusive.

4. Compounds of the general formula:

S.(CH2) s;1 TR 2X- 1 l. in which R, R, R, R and R? are each an alkyl group and X is n nx a o h ota umbe of ca n atom in the cation being from 11 to 16 inclusive.

5. Non-toxic salts of 1diethylsulphonium-4-triethylammonium-butane.

6. Non-toxic salts of 1-ethylmethylsulphonium-4-ethyldi-n-propyl-ammoniumbutane.

7. Non-toxic salts of 1-methy1isopropylsulphonium- 4-methyldi-iso-propylammoniumbutane.

8. Non-toxic salts of 1-diethylsulphonium-5-triethylammonium-pentane.

9. Non-toxic salts of l-ethylmethylsulphoniumJ-ethyldi-n-propylammoniumpentane.

References Cited in the file of this patent UNITED STATES PATENTS Rieveschl Oct. 9, 1949 Morrison et a1. Aug. 11, 1953 Mahan Sept. 21, 1954 OTHER REFERENCES Schneider et 3].: Ann. 392, pp. 3 and (1912). 

1. COMPOUNDS OF THE GENERAL FORMULA: 